A National Institute of Environmental Health Sciences Center in Molecular and Cellular Toxicology with Human Applications is proposed with the overall objective of coordinating and stimulating interdisciplinary interactions and collaborations between established investigators conducting high quality research and clinical studies on the effects of environmental factors on human health. More than 4,000 human disorders have been attributed to genetic alterations to date and, of these, approx. 700 have been mapped to specific chromosomes with approx. 300 of the mutant genes cloned and sequenced. Because most of the human genome will be sequenced in the next decade and since many environmental agents either damage genes directly, or alter gene expression and/or cell function, the focus of this Center will be on research and clinical studies which examine the influence of environmental factors on human health and disease at the molecular and cellular level and on dissemination of knowledge in toxicology to the general public. To accomplish these objectives, we have developed a series of four integrated research cores on the Regulation of Gene Expression, Signal-transduction, Reproduction/Development/Aging and Human Exposure and Disease. A series of five facility cores have been developed to assist members of the Center in their research programs and to support, enhance and stimulate the professional development of the Center. These support facilities, which include a Transgenic Animal Facility, an In Situ Hybridization/Immunocytochemistry Facility, a Cell Culture Facility, a Cell Imaging Facility, and an Epidemiology/Biostatistics/Informatics/Computer Support Facility, are intended to provide members of the Center general support in the conduct and expansion of their research progrlams by making available on temporary approaches in toxicology research and assisting in technology transfer. Enrichment programs consisting of, but not limited to, seminar series, annual thematic symposia, visiting professorships, etc., as well as an aggressive pilot project program will be employed to stimulate continued growth and development of the Center and its interdisciplinary research programs on environmental factors affecting human health. A Community Outreach Program will be developed and maintained which will consist of review courses or workshops offered to local, state, national and international participants, as well as educational programs at the middle school, high school, undergraduate and graduate levels. The high school program will be accomplished in concert with the NIH-funded Minority High School Student Research Apprenticeship Program in which members of the Center participate and which receives supplemental support from the Wayne State University Institute of Chemical Toxicology. Presentations and discussions of contemporary issues in toxicology (e.g. heavy metals (Pb); solvents, etc.) will be conducted and made available to the general public via the University-operated radio station, WDET. The center will receive guidance from an Internal Advisory Board which will provide advice on research direction, facility support, and enrichment programs and by an External Advisory Committee which will provide a more comprehensive view on Center progress and will review and rank submitted pilot project proposals.